1. Field of the Invention
The teachings provided herein relate to the preparation and uses of formulations comprising a serotonergic agent or a dopaminergic agent for oral transmucosal delivery using a taste titration.
2. Description of Related Art
The monoamines dopamine and serotonin are major central nervous system neurotransmitters. Their deficiencies in the CNS or imbalance are associated with multiple disorders. Multiple medications have been used therapeutically to increase the levels of dopamine and serotonin in the central nervous system.
In 1971, President Nixon declared a “war on drugs.” It has not gone well. For the last decade, the direct and indirect costs to society of drug and alcohol abuse in the United States alone has approached $4 trillion. In the United States, since 1998, there have been more than 30,000 drug-related homicides, as well as 250,000 alcohol-related vehicular deaths, and that is just the beginning. One cannot forget the anonymous personal tragedies that never hit the charts. The abuse of illicit drugs such as psychostimulants, for example, is a problem worldwide, and few treatments are available for treating such drug abuse and addiction. Monoamine releasers have been used as agonists to attempt treatment of cocaine addiction and alleviate withdrawal symptoms, as well as relapse. Unfortunately, some of the treatments also possess the potential for abuse due to the activation of mesolimbic dopamine neurons in reward pathways. It's been suggested that serotonin administration may be administered to offset this problem, such that achieving a dopamine/serotonin balance could be a successful treatment regime for such addictions. Rothman, et al., have studied various agonist therapies on rats and monkeys, with limited success, in which the research directed to discovering single molecule agonists that are dual releasers of both dopamine and serotonin. See Rothman, et al. Ann. N.Y. Acad. Sci. 1074:245-260 (2006); see also Rothman, et al. Exp Clin Psychopharmacol. 16(6):458-74 (2008).
Treatments directed to addressing serotonin and dopamine deficits have also been used for affective disorders, attention deficit disorder, attention deficit hyperactivity disorder, and autism. Unfortunately, there have been a number of problems associated with currently available treatments, such as not knowing the levels of agent that need to be administered for a particular patient, overdosing administration of agents, achieving a neurotransmitter imbalance, and long wait-times to determine effectiveness of a given treatment. Doctors have had to monitor patients very closely to make adjustments and estimate the proper balance between the neurotransmitters. And, it doesn't help that many activities of daily life also affect the neurotransmitter balance and add to the guesswork, such as food intake, stress, exercise, drugs taken, and the like. For example, when administering selective serotonin reuptake inhibitors (SSRIs), doctors tell patients that it will take a month before they know if the treatment is effective. In addition, overdoses that occur through such treatments have been suggested as the cause of suicides, since the overdoses can exacerbate some disorders. Sometimes other drugs must be added to current treatment methods to treat side effects, and sometimes these additional drugs have their own side effects.
One of skill will appreciate formulations, systems, and methods of administering serotonergic agents and dopaminergic agents that have the ability to remit deficiencies and imbalances in a subject's serotonin and dopamine levels. One of skill will particularly appreciate formulations, systems, and methods of administering serotonergic agents and dopaminergic agents that reduce or remove the guesswork associated with current therapies, as well as the side effects that may also be experienced. The formulations, systems, and methods taught herein provide several advantages over the state-of-the art, such that they at least enable (1) the patient and doctor to readily determine the correct dosages, (2) a quick measure of effectiveness of a treatment, (3) a use of a chemical pathway that is desirable, (4) a quick delivery of the agents across the blood-brain barrier through the use of oral transmucosal delivery, minimizing the amount of free metabolites circulating in the body, (5) an inherent adjustment in the amounts of agents administered to compensate for changes in the level of imbalance in neurotransmitter levels, (6) a non-frightening and pleasant treatment for many disorders suffered by a patient, (7) a mitigated risk of overdose to a patient through the simple taste response, and (8) an easy identification of the correct neurotransmitter balance in the subject by the doctor and the patient.